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Christopher Alexander French, MD
Associate Pathologist, Brigham and Women's Hospital
Associate Professor of Pathology, Harvard Medical School

Brigham and Women's Hospital
Department of Pathology
75 Francis Street
Boston, MA 02115

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Research Narrative:

Our laboratory is focused on the NUT midline carcinoma (NMC), an uncommon, but invariably lethal carcinoma of children and adults that effects midline structures, including sinonasal passages, upper respiratory tract, proximal lung, mediastinum, and bladder. The NMC is defined by chromosomal rearrangement of the NUT oncogene on chromosome 15, which in 2/3rds of tumors is fused to BRD4 on chromosome 19, but in the remaining tumors is fused to another partner gene, including BRD3, encoding chimeric fusion oncoproteins. We have shown that BRD-NUT oncoproteins block differentiation and maintain the growth of NMC cells. The overall goals of our lab are to 1. determine the oncogenic mechanisms of BRD-NUT oncoproteins, and 2. identify drug target(s) for more effective treatment if the disease. To facilitate this, we have developed an inducible transgene system for mapping functional domains of BRD-NUT, as well as identification of interacting proteins. Further, we are using this inducible system to express NUT shRNA as a positive control in a multi-drug screen for identification of potential drug targets for treatment of this disease.